The long-term objective of this project is to contribute to understanding of the regulation of the rate of urea synthesis and the stabilization of blood pH. The experiments to be done will test further the working hypothesis that disposal of bicarbonate is a major physiological function of ureagenesis, and that the pH of blood and interstitial fluid is regulated in part by the rate at which the liver consumes bicarbonate in ureagenesis. Rat livers will be perfused with media containing normal constituents of portal blood, the concentrations of which will be varied over the reported portal range, and the rate of synthesis of urea, the net consumption or production of glutamine, the uptake of ammonium ion, and the net uptake or release of individual amino acids will be measured. High-pressure liquid chromatographic methods will be used for assay of the perfusing medium and the perfusate after traversing the liver. Management of blood pH is often a clinical problem. The approaches currently used are semi-empirical. More fundamental understanding of the factors that are involved in the maintenance of pH homeostasis should lead to more flexible and effective treatment in such cases.